Bartter

Type 1 Bartter syndrome causes hypokalaemia and metabolic alkalosis owing to mutation in the SLC12A1 gene. Meanwhile, hypocalcaemia is rare in Bartter syndrome, except in type 5 Bartter syndrome. Herein, we describe two siblings with type 1 Bartter syndrome with recurrent transient severe hypocalcaemia. They each visited our hospital several times with chief complaints of numbness in the limbs, shortness of breath and tetany after stresses such as exercise or fever. Severe hypocalcaemia was also observed with a serum calcium level of approximately 6...

The introduction of newborn screening for cystic fibrosis (CF) increased diagnosis of cystic fibrosis screen positive inconclusive diagnosis (CFSPID). We described the case of a 12-month-old boy with CFSPID who, during summer, presented Pseudo-Bartter syndrome with no diagnostic criteria for CF.

Mitochondria play a key role in kidney physiology and pathology. They produce ATP to fuel energy-demanding water and solute reabsorption processes along the nephron. Moreover, mitochondria contribute to cellular health by the regulation of autophagy, (oxidative) stress responses, and apoptosis. Mitochondrial abundance is particularly high in cortical segments, including proximal and distal convoluted tubules. Dysfunction of the mitochondria has been described for tubulopathies such as Fanconi, Gitelman, and Bartter-like syndromes and renal tubular acidosis...

The tubular system of the kidneys is a complex series of morphologic and functional units orchestrating the content of tubular fluid as it flows along the nephron and collecting ducts. Renal tubules maintain body water, regulate electrolytes and acid-base balance, reabsorb precious organic solutes, and eliminate specific metabolites, toxins, and drugs. In addition, decisive mechanisms to adjust blood pressure are governed by the renal tubules. Genetic as well as acquired disorders of these tubular functions may cause serious diseases that manifest both in childhood and adulthood...

Bartter syndrome is a group of rare genetic disorders that compromise kidney function by impairing electrolyte reabsorption. Left untreated, the resulting hyponatremia, hypokalemia, and dehydration can be fatal, and there is currently no cure. Bartter syndrome type II specifically arises from mutations in KCNJ1, which encodes the renal outer medullary potassium channel, ROMK. Over 40 Bartter syndrome-associated mutations in KCNJ1 have been identified, yet their molecular defects are mostly uncharacterized. Nevertheless, a subset of disease-linked mutations compromise ROMK folding in the endoplasmic reticulum (ER), which in turn results in premature degradation via the ER associated degradation (ERAD) pathway...

Bartter syndrome type 1 is caused by mutations in the solute carrier family 12 member 1 ( SLC12A1 ), encoding the sodium-potassium-chloride cotransporter-2 (NKCC2). In addition to causing renal salt-losing tubulopathy, SLC12A1 mutations are known to cause nephrocalcinosis due to hypercalciuria, as well as failure to thrive associated with abnormal calcium and phosphorus homeostasis. We report a now 7-year-old Japanese girl with polyuria, hyponatremia, hypokalemia, and metabolic alkalosis, in whom compound heterozygous novel SLC12A1 mutations were identified...

Epithelial transport is a multifaceted process crucial for maintaining normal physiological functions in the human body. This comprehensive review delves into the pathophysiological mechanisms underlying epithelial transport and its significance in disease pathogenesis. Beginning with an introduction to epithelial transport, it covers various forms, including ion, water, and nutrient transfer, followed by an exploration of the processes governing ion transport and hormonal regulation. The review then addresses genetic disorders, like cystic fibrosis and Bartter syndrome, that affect epithelial transport...

Cystic fibrosis (CF) is a multiorgan disease, caused by autosomal recessive (AR) mutations in the cystic fibrosis transmembrane regulator (CFTR) acting primarily as a chloride channel. CF is most commonly diagnosed in Caucasian populations. Common clinical presentations in pediatric patients include chronic cough, respiratory tract infections such as pneumonia, digestive symptoms, and stunted growth, and malnutrition due to gastrointestinal malabsorption and pancreatic insufficiency. Excessive sweat sodium chloride losses due to dysfunctional sweat glands in CFTR result in volume contraction and secondary hyperaldosteronism leading to renal potassium losses and metabolic alkalosis...

In a patient with persistent hypokalemia, it is important to consider Gitelman syndrome, a rare, salt-wasting tubulopathy inherited in an autosomal recessive pattern. Gitelman syndrome leads to electrolyte abnormalities like hypokalemia, hypomagnesemia, and metabolic alkalosis. Typical clinical features include muscle cramps, fatigue, polydipsia, and salt cravings. Our case involves a female patient in her early 40s who visited the endocrinology clinic with symptoms of polyuria, constipation, muscle weakness, and fatigue...

BACKGROUND: Rett syndrome (RTT) is now widely recognized as a profound neurological disorder that predominantly affects females and is closely associated with mutations in the methylated CpG binding protein 2 (MECP2) gene located on the X chromosome. The Characteristic symptoms of RTT include the loss of acquired language and motor skills, repetitive hand movements, irregular breathing, and seizures. Additionally, RTT patients may experience sporadic episodes of gastrointestinal problems, hypoplasia, early-onset osteoporosis, bruxism, and screaming episodes...

Background and Objectives : Bartter syndrome (BS) is a rare group of autosomal-recessive disorders that usually presents with hypokalemic metabolic alkalosis, occasionally with hyponatremia and hypochloremia. The clinical presentation of BS is heterogeneous, with a wide variety of genetic variants. The aim of this systematic review was to examine the available literature and provide an overview of the case reports and case series on BS. Materials and Methods : Case reports/series published from April 2012 to April 2022 were searched through Pubmed, JSTOR, Cochrane, ScienceDirect, and DOAJ...

Bartter's syndrome (BS) is a rare group of hereditary salt losing tubulopathies due to impairment of renal transport mechanism. Herein, we report a boy in early childhood who was diagnosed to have infantile Bartter's syndrome. Laboratory investigations revealed hypokalaemia and metabolic alkalosis which was managed with oral potassium chloride supplementation. The inner ear showed no anatomical abnormalities. Sequential cochlear implantation was performed 4 months apart. Postoperative electrical stimulation yielded good response and a symmetric mapping...

Pseudo-Bartter's (PB) syndrome is characterized by hypokalemic metabolic alkalosis and failure to thrive which constitutes a rare but typical presentation of cystic fibrosis (CF) in children. The most common mutation of CF is F508del, due to loss of 3 base pairs, causing deletion of phenylalanine, at position 508. We present a case of CF presenting with failure to thrive, dehydration, PB syndrome associated with urosepsis and primo-colonization with Escherichia coli suggesting the role of epigenetic factors...

UNLABELLED: There is limited information available on the clinical data, sweat test trends, and outcomes of individuals with cystic fibrosis (CF) who present with an isolated episode of hypoelectrolytemia with metabolic alkalosis (HMA). This study describes a cohort of Italian individuals with HMA as presenting symptom. The study is a retrospective multicenter analysis of individuals who presented with HMA as an initial symptom and was followed at 8 Italian CF Centers, from March 1988 to March 2022...

BACKGROUND: The genetic tubulopathies are rare and heterogenous disorders that are often difficult to identify. This study examined the tubulopathy-causing genes for ocular associations that suggested their genetic basis and, in some cases, the affected gene. METHODS: Sixty-seven genes from the Genomics England renal tubulopathy panel were reviewed for ocular features, and for retinal expression in the Human Protein Atlas and an ocular phenotype in mouse models in the Mouse Genome Informatics database...

Melanoma-associated antigen D2 (MAGED2) plays an essential role in activating the cAMP/PKA pathway under hypoxic conditions, which is crucial for stimulating renal salt reabsorption and thus explaining the transient variant of Bartter's syndrome. The cAMP/PKA pathway is also known to regulate autophagy, a lysosomal degradation process induced by cellular stress. Previous studies showed that two members of the melanoma-associated antigens MAGE-family inhibit autophagy. To explore the potential role of MAGED2 in stress-induced autophagy, specific MAGED2-siRNA were used in HEK293 cells under physical hypoxia and oxidative stress (cobalt chloride, hypoxia mimetic)...

BACKGROUND: Hereditary renal tubular disorders (HRTD) represent a group of genetic diseases characterized by disturbances in fluid, electrolyte, and acid-base homeostasis. There is a paucity of studies on pediatric HRTD in Egypt. In this study, we aimed to study the pattern, characteristics, and growth outcome of HRTD at an Egyptian medical center. METHODS: This study included children from one month to < 18-years of age with HRTD who were diagnosed and followed up at the Pediatric Nephrology Unit of Sohag University Hospital from January 2015 to December 2021...

BACKGROUND: Long-read sequencing is increasingly used to uncover structural variants in the human genome, both functionally neutral and deleterious. Structural variants occur more frequently in regions with a high homology or repetitive segments, and one rearrangement may predispose to additional events. Bartter syndrome type 3 (BS 3) is a monogenic tubulopathy caused by deleterious variants in the chloride channel gene CLCNKB, a high proportion of these being large gene deletions. Multiplex ligation-dependent probe amplification, the current diagnostic gold standard for this type of mutation, will indicate a simple homozygous gene deletion in biallelic deletion carriers...

BACKGROUND: Bartter syndrome (BS) is a rare congenital salt-losing renal tubular transport disorder, characterized by salt wasting, polyuria, biochemical abnormalities, and acid-base homeostasis imbalance. The syndrome has five different genetic forms, and novel mutations of CLCNKB gene lead to type 3 BS also known as classic BS. In this case, we report clinical and molecular findings from a newborn baby with BS. CASE: A 10-day-old male infant born at 37 weeks of gestation by cesarean section following a pregnancy complicated with polyhydramnios, and fetal distress to a 30-year-old gravida 3, para 3 mother, with a 2500 g birth weight was brought to the pediatric emergency department due to weight loss and jaundice...

Gitelman syndrome (GS) is a rare renal tubulopathy with an autosomal recessive mode of inheritance, caused by biallelic pathogenic variants in the SLC12A3 gene. The clinical features may overlap with other disorders, such as Bartter syndrome type 3, HNF1B nephropathy or even mitochondrial disease, but can be distinguished by molecular genetic analysis. Here we report on two preschool brothers, who presented with a several months' history of episodes of carpopedal spasms and muscle aches. The biochemical analyses revealed hypokalemia and hypomagnesemia without metabolic alkalosis...